Hypointense foci in the medial temporal lobe may reflect
Alzheimer’s pathology. To discern the etiology of iron
accumulation in Alzheimer’s disease, we performed
high-resolution GRE imaging at 7.0T of AD specimens. We
registered and evaluated concurrent DAB-iron,
CD163-microglia, and beta-amyloid stains of the same
specimens. Iron containing foci best explained the MR
hypointense foci that accumulated at and along the
undersurface of the CA1/subiculum junction. This iron
was primarily localized within microglia, not amyloid
plaques.

Brain atrophy is considered a biomarker of Alzheimer's
disease (AD) pathology. However, mixed pathologies are
common in the elderly, and several of them may lead to
atrophy. Also, only a handful of studies with low
numbers of participants have combined brain MR volumetry
with measures of neuropathology obtained after death.
Thus, the relation between brain atrophy and age-related
neuropathology is actually not well-established. The
purpose of this investigation was to assess the
neuropathologic correlates of regional brain volumes by
combining ex-vivo MR volumetry and pathology information
on a large community cohort of older persons.

The purpose of this study is to investigate the
relationship between pseudo-continuous ASL (pCASL)
perfusion and the parameters of relative perfusion (R1)
and tracer distribution volume ratio (DVR) derived from
PiB-PET in 25 familial Alzheimer¡¯s disease related
subjects. The spatial patterns between pCASL CBF and
PiB-PET R1 are highly consistent with significant
voxel-wise correlations, whereas the correlation between
pCASL perfusion and PiB-PET DVR is negative across
subjects. Our study supports the validity of both pCASL
and PiB-PET as imaging markers of Alzheimer¡¯s disease.

10:36

0489.

Functional connectivity of
the primary olfactory cortex is decreased in Alzheimer’s
disease and mild cognitive impairment

Olfactory deficits are known to occur in patients with
mild cognitive impairment (MCI) and early Alzheimer’s
disease. In this work, we performed olfactory functional
magnetic resonance imaging of the primary olfactory
cortex and demonstrated that the primary olfactory
cortex is involved functionally in early Alzheimer’s
disease.

A specific combination of omega-3 fatty acids with
precursors and cofactors in membrane synthesis was
developed for the dietary management of AD, specifically
to enhance the formation of neuronal membranes and
synapses. In this study, we tested the hypothesis that a
specific multi-nutrient diet is able to positively
influence brain connectivity and vascular health in a
mouse model for AD vascular risk factor (apoE4). Resting
state functional MRI and cerebral blood flow were
assessed by MRI at 11.7T. Results showed enhanced
perfusion, increased neural connectivity; and increased
number of post-synapses in animals fed with a
multi-nutrient diet.

Ai-Ling Lin1,2, Wei Zhang1, and
Arlan Richardson21Research Imaging Institute, University of
Texas Health Science Center at San Antonio, San Antonio,
TX, United States,2Cellular
& Structural Biology, University of Texas Health Science
Center at San Antonio, San Antonio, TX, United States

In the study, we used multi-metric MRI methods to
evaluate the treatment efficacy of rapamycin on
cerebrovascular functions in mice expressing the human
e4 allele of the apolipoprotein E gene (APOE4), which is
a risk factor for Alzheimer’s disease (AD). We found
that young APOE4 mice treated with rapamycin had
significantly restored cerebral blood flow and blood
brain barrier integrity compared to the non-treated
group, and the effects were prominent over time. The
restored cerebrovascular functions in the APOE4 mice
resembled those of age-matched wild-type mice. Our
results suggest that rapamycin would be promising for
future treatment/prevention of AD.

Rachelle Crescenzi1,2, Catherine DeBrosse1,2,
Ravi Prakash Reddy Nanga2, Hari Hariharan2,
Ari Borthakur2, John Detre3,
Virginia M.-Y. Lee4, and Ravinder Reddy21Biochemistry and Molecular Biophysics,
University of Pennsylvania, Philadelphia, PA, United
States,2Center
for Magnetic Resonance and Optical Imaging (CMROI),
University of Pennsylvania, Philadelphia, PA, United
States,3Center
for Functional Neuroimaging (CfN), University of
Pennsylvania, Philadelphia, PA, United States,4Center
for Neurodegenerative Disease Research (CNDR),
University of Pennsylvania, Philadelphia, PA, United
States

Synapse loss is the main correlate of cognitive defecits
in AD. Here, synapse loss in the sub-regions of the
hippocampus of the P301S tauopathic mouse brain is shown
to correlate with glutamate loss measured by GluCEST:
glutamate chemical exchange saturation transfer. Average
GluCEST is decreased in the thalamus/hypo-thalamus and
CA sub-region of the hippocampus, yet maintained in the
dentate gyrus. Immunohistochemistry confirms that
synapse loss occurs throughout the transgenic brain,
except in the DG where neurons are known to be
regenerated. GluCEST imaging allows the DG neuronal
integrity to be observed in vivo, which was not possible
using conventional spectroscopy.

11:36

0493.

Perfusion and vascular
response as early markers in a bigenic mouse model of
Alzheimer’s Disease

Tempoparietal hypoperfusion is an early symptom of
Alzheimer’s Disease (AD). Recent studies in AD and mild
cognitive impairment (MCI) patients also suggest that
the cerebrovascular response to hypercapnia (CVR) may be
a more sensitive readout. We performed arterial spin
labeling to determine cerebral blood flow increases in
response to a hypoventilation-induced hypercapnic
challenge in a bigenic biAT mice, a model for AD. We
report decreased basal perfusion already at young age (3
months), as well as a significantly increased CVR in
response to hypoventilation-induced hypercapnia.

Amyloid deposits occur many years before
neuropsychological symptoms of Alzheimer's disease.
Their detection by MRI is thus critical. We designed a
contrast agent combining the properties of VHH
antibodies and gadolinium to specifically label amyloid
plaques by MRI. We showed that hypointense spots were
observed on T2* images followingin
vitroincubation
orin vivoICV
injection of the VHH-DOTA/Gd. Several spots were
colocalized with the amyloid plaques revealed by a
reference (Gold-standard) Gd-staining procedure.
Overall, this study describes a new promising tool for
the detection of amyloid deposits by MRI.

This work analyses structural and physiological features
in a healthy population (25 subjects, PAD group) in risk
of developing Alzheimer's disease (left and right
hippocampus mean-2std.) the asl technique provides
perfusion maps that, after normalization and partial
volume effect correction steps, are studied through a
two-sample t-test (25 subjects control group). also,
segmented 3dt1w images with vbm-dartel. pad, as
expected, suffer from grey matter loss in both
hippocampi and, additionally, hypoperfusion hippocampi,
amygdala entorhinal cortex. we propose to include
studies, more sensitive than structural vbm, standard
research criteria for early diagnosis of ad.